Digital Commons Network^™

How Do Low-Income Single-Mothers Get By When Unemployment Strikes: Patterns Of Multiple Program Participation After Transition From Employment To Unemployment, Chi-Fang Wu, Yu-Ling Chang, Soohyun Yoon, Salma Musaad

Children’s Nutrition Research Center Staff Publications

Little is known about longitudinal patterns of welfare program participation among single mothers after they transition from employment to unemployment. To better understand how utilization patterns of these welfare programs may change during the 12 months after a job loss, we used the 2008 Survey of Income and Program Participation to examine the patterns of participation in Medicaid, the Supplemental Nutrition Assistance Program, Temporary Assistance for Needy Families, and unemployment insurance among 342 single mothers who transitioned from employment to unemployment during the Great Recession. Using sequence analysis and cluster analysis, this paper identified four distinct patterns of program participation: …

New Natural Compound Inhibitors Of Pdgfra (Platelet-Derived Growth Factor Receptor Α) Based On Computational Study For High-Grade Glioma Therapy, Wenzhuo Yang, Shengnan Wang, Xiangmao Zhang, Hu Sun, Menghan Zhang, Hongyu Chen, Junxiang Cui, Jinyang Li, Fei Peng, Mingqin Zhu, Bingcheng Yu, Yifan Li, Liu Yang, Wanwan Min, Mengru Xue, Lin Pan, Hao Zhu, Bo Wu, Yinghao Gu

Children’s Nutrition Research Center Staff Publications

Background: High-grade glioma (HGG) is a malignant brain tumor that is common and aggressive in children and adults. In the current medical paradigm, surgery and radiotherapy are the standard treatments for HGG patients. Despite this, the overall prognosis is still very bleak. Studies have shown that platelet-derived growth factor receptor α (PDGFRA) is an essential target to treat tumors and inhibiting the activity of PDGFRA can improve the prognosis of HGG. Thus, PDGFRA inhibitors are critical to developing drugs and cancer treatment.

Objective: The purpose of this study was to screen lead compounds and candidate drugs with potential inhibitors against …

Bibliometric And Visual Analysis Of Research On The Links Between The Gut Microbiota And Pain From 2002 To 2021, Menghan Mao, Yanyu Zhou, Yingfu Jiao, Suqing Yin, Chiwai Cheung, Weifeng Yu, Po Gao, Liqun Yang

Children’s Nutrition Research Center Staff Publications

Background and aims: The gut microbiota is involved in the regulation of pain, which is proved by plenty of evidence. Although a substantial quantity of research on the link between the gut microbiota and pain has emerged, no study has focused on the bibliometric analysis of this topic. We aim to present a bibliometric review of publications over the past 20 years and predict research hot spots.

Methods: Relevant publications between 2002 and 2021 were extracted from the Science Citation Index-Expanded (SCI-EXPANDED) of the Web of Science Core Collection (WoSCC) database on April 22, 2022. CiteSpace (version 5.8 R3c), VOSviewer, …

Developing And Predicting Of Early Mortality After Endovascular Thrombectomy In Patients With Acute Ischemic Stroke, Yimin Chen, Sijie Zhou, Shuiquan Yang, Mohammad Mofatteh, Yuqian Hu, Hongquan Wei, Yuzheng Lai, Zhiyi Zeng, Yajie Yang, Junlin Yu, Juanmei Chen, Xi Sun, Wenlong Wei, Thanh N Nguyen, José Fidel Baizabal-Carvallo, Xuxing Liao

Children’s Nutrition Research Center Staff Publications

Background: Stroke is one of the leading causes of mortality across the world. However, there is a paucity of information regarding mortality rates and associated risk factors in patients with acute ischemic stroke (AIS) undergoing endovascular thrombectomy (EVT). In this study, we aimed to clarify these issues and analyzed previous publications related to mortality in patients treated with EVT.

Methods: We analyzed the survival of 245 consecutive patients treated with mechanical thrombectomy for AIS for which mortality information was obtained. Early mortality was defined as death occurring during hospitalization after EVT or within 7 days following hospital discharge from the …

Patent Foramen Ovale In Children: Unique Pediatric Challenges And Lessons Learned From Adult Literature, Sunil Saharan, Joseph Vettukattil, Aarti Bhat, Venu Amula, Manish Bansal, Devyani Chowdhury, Umesh Dyamenahalli, Saurabh Kumar Gupta, Bibhuti Das, T K Susheel Kumar, Ashok Muralidaran, Kalyani Trivedi, Sethuraman Swaminathan, Neha Bansal, Unnati Doshi, Arvind Hoskoppal, Seshadri Balaji

Faculty, Staff and Students Publications

A patent foramen ovale (PFO) is a frequent incidental finding during echocardiography in otherwise healthy children. In most healthy children with a diagnosis of isolated incidental PFO, no further follow-up or intervention is necessary. In some children, PFO is associated with certain clinical syndromes such as cryptogenic stroke, decompression sickness, migraine, and platypnea-orthodeoxia syndrome. This review discusses PFO anatomy, diagnostic imaging, PFO-associated clinical situations, management options, and the role of PFO in certain congenital heart disease. This review also highlights the current deficiency of pediatric data guiding management of these uncommon but important PFO-associated conditions. Future multicenter randomized controlled studies …

Comprehensive Improvement Of Cardiology Inpatient Transfers: A Bed-Availability Triggered Approach, Judson A Moore, Lindsay F Eilers, Amanda J Willis, Michael D Chance, Julie A La Salle, Ellen H Delgado, Katie M Bien, Jordana R Goldman, Shreya S Sheth

Faculty, Staff and Students Publications

INTRODUCTION: Patient transfers pose a potential risk during hospitalizations. Structured communication practices are necessary to ensure effective handoffs, but occur amidst competing priorities and constraints. We sought to design and implement a multidisciplinary process to enhance communication between pediatric cardiovascular intensive care unit and cardiology floor teams with a comprehensive approach evaluating efficiency, safety, and culture.

METHODS: We conducted a prospective quality improvement study to enact a bed-availability triggered bedside handoff process. The primary aim was to reduce the time between handoff and unit transfer. Secondary metrics captured the impact on safety (reported safety events, overnight transfers, bounce backs, and …

The Nhlbi Study On Long-Term Outcomes After The Multisystem Inflammatory Syndrome In Children (Music): Design And Objectives, Dongngan T Truong, Felicia L Trachtenberg, Gail D Pearson, Audrey Dionne, Matthew D Elias, Kevin Friedman, Kerri H Hayes, Lynn Mahony, Brian W Mccrindle, Matthew E Oster, Victoria Pemberton, Andrew J Powell, Mark W Russell, Lara S Shekerdemian, Mary Beth Son, Michael Taylor, Jane W Newburger

Faculty, Staff and Students Publications

BACKGROUND: The Long-terM OUtcomes after the Multisystem Inflammatory Syndrome In Children (MUSIC) study aims to characterize the frequency and time course of acute and long-term cardiac and non-cardiac sequelae in multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C), which are currently poorly understood.

METHODS: This multicenter observational cohort study will enroll at least 600 patientsyears, and optional genetic testing. Cardiac imaging at specific time points includes standardized echocardiographic assessment (all participants) and cardiac magnetic resonance imaging (CMR) in those with left ventricular ejection fraction (LVEF)

CONCLUSION: The MUSIC study, with the largest cohort of MIS-C patients and the longest …

Current State Of The Art In Hypoplastic Left Heart Syndrome, Aditya K Birla, Sunita Brimmer, Walker D Short, Oluyinka O Olutoye, Jason A Shar, Suriya Lalwani, Philippe Sucosky, Anitha Parthiban, Sundeep G Keswani, Christopher A Caldarone, Ravi K Birla

Faculty, Staff and Students Publications

Hypoplastic left heart syndrome (HLHS) is a complex congenital heart condition in which a neonate is born with an underdeveloped left ventricle and associated structures. Without palliative interventions, HLHS is fatal. Treatment typically includes medical management at the time of birth to maintain patency of the ductus arteriosus, followed by three palliative procedures: most commonly the Norwood procedure, bidirectional cavopulmonary shunt, and Fontan procedures. With recent advances in surgical management of HLHS patients, high survival rates are now obtained at tertiary treatment centers, though adverse neurodevelopmental outcomes remain a clinical challenge. While surgical management remains the standard of care for …

Artificial Intelligence In The Pediatric Echocardiography Laboratory: Automation, Physiology, And Outcomes, Minh B Nguyen, Olivier Villemain, Mark K Friedberg, Lasse Lovstakken, Craig G Rusin, Luc Mertens

Faculty, Staff and Students Publications

Artificial intelligence (AI) is frequently used in non-medical fields to assist with automation and decision-making. The potential for AI in pediatric cardiology, especially in the echocardiography laboratory, is very high. There are multiple tasks AI is designed to do that could improve the quality, interpretation, and clinical application of echocardiographic data at the level of the sonographer, echocardiographer, and clinician. In this state-of-the-art review, we highlight the pertinent literature on machine learning in echocardiography and discuss its applications in the pediatric echocardiography lab with a focus on automation of the pediatric echocardiogram and the use of echo data to better …

Optimal Fenestration Of The Fontan Circulation, Zan Ahmad, Lynn H Jin, Daniel J Penny, Craig G Rusin, Charles S Peskin, Charles Puelz

Faculty, Staff and Students Publications

In this paper, we develop a pulsatile compartmental model of the Fontan circulation and use it to explore the effects of a fenestration added to this physiology. A fenestration is a shunt between the systemic and pulmonary veins that is added either at the time of Fontan conversion or at a later time for the treatment of complications. This shunt increases cardiac output and decreases systemic venous pressure. However, these hemodynamic benefits are achieved at the expense of a decrease in the arterial oxygen saturation. The model developed in this paper incorporates fenestration size as a parameter and describes both …

An Automated Risk Index For Diabetic Ketoacidosis In Pediatric Patients With Type 1 Diabetes: The Ri-Dka, David D Schwartz, Rosa Banuelos, Serife Uysal, Mili Vakharia, Kristen R Hendrix, Kelly Fegan-Bohm, Sarah K Lyons, Rona Sonabend, Sheila K Gunn, Selorm Dei-Tutu

Faculty, Staff and Students Publications

Identifying patients at high risk for diabetic ketoacidosis (DKA) is crucial for informing efforts at preventive intervention. This study sought to develop and validate an electronic medical record (EMR)-based tool for predicting DKA risk in pediatric patients with type 1 diabetes. Based on analysis of data from 1,864 patients with type 1 diabetes, three factors emerged as significant predictors of DKA: most recent A1C, type of health insurance (public vs. private), and prior DKA. A prediction model was developed based on these factors and tested to identify and categorize patients at low, moderate, and high risk for experiencing DKA within …

Paraventricular Vitamin D Receptors Are Required For Glucose Tolerance In Males But Not Females, Jessie Beck, Silvania Da Silva Teixeira, Keisha Harrison, Gabrielle Phillips, Yanlin He, Stephanie Sisley

Faculty, Staff and Students Publications

When delivered directly into the brain, vitamin D, can improve glucose levels in male mice. Additionally, the loss of the vitamin D receptor (VDR) in male mice's paraventricular hypothalamus (PVH) results in impaired glucose tolerance. Data in humans shows that low vitamin D levels are detrimental to glucose homeostasis, an effect that may be more prominent in men. However, it is unknown if vitamin D action in the brain is required for normal glucose regulation in female mice. This study shows that in both viral and genetic models, male mice with obesity and PVH VDR loss have impaired glucose tolerance …

The Burden Of Critical Illness In Hospitalized Children In Low- And Middle-Income Countries: Protocol For A Systematic Review And Meta-Analysis, Teresa B Kortz, Katie R Nielsen, Rishi P Mediratta, Hailey Reeves, Nicole F O'Brien, Jan Hau Lee, Jonah E Attebery, Emaan G Bhutta, Carter Biewen, Alvaro Coronado Munoz, Mary L Dealmeida, Yudy Fonseca, Shubhada Hooli, Hunter Johnson, Niranjan Kissoon, Mara L Leimanis-Laurens, Amanda M Mccarthy, Carol Pineda, Kenneth E Remy, Sara C Sanders, Yemisi Takwoingi, Matthew O Wiens, Adnan T Bhutta

Faculty, Staff and Students Publications

BACKGROUND: The majority of childhood deaths occur in low- and middle-income countries (LMICs). Many of these deaths are avoidable with basic critical care interventions. Quantifying the burden of pediatric critical illness in LMICs is essential for targeting interventions to reduce childhood mortality.

OBJECTIVE: To determine the burden of hospitalization and mortality associated with acute pediatric critical illness in LMICs through a systematic review and meta-analysis of the literature.

DATA SOURCES AND SEARCH STRATEGY: We will identify eligible studies by searching MEDLINE, EMBASE, CINAHL, and LILACS using MeSH terms and keywords. Results will be limited to infants or children (ages >28 …

The Autophagic Protein P62 Is A Target Of Reactive Aldehydes In Human And Murine Cholestatic Liver Disease, Colin T Shearn, Aimee L Anderson, Michael W Devereux, David J Orlicky, Cole Michel, Dennis R Petersen, Colin G Miller, Sanjiv Harpavat, Edward E Schmidt, Ronald J Sokol

Faculty, Staff and Students Publications

Inflammatory cholestatic liver diseases, including Primary Sclerosing Cholangitis (PSC), are characterized by periportal inflammation with progression to cirrhosis. The objective of this study was to examine interactions between oxidative stress and autophagy in cholestasis. Using hepatic tissue from male acute cholestatic (bile duct ligated) as well as chronic cholestatic (Mdr2KO) mice, localization of oxidative stress, the antioxidant response and induction of autophagy were analyzed and compared to human PSC liver. Concurrently, the ability of reactive aldehydes to post-translationally modify the autophagosome marker p62 was assessed in PSC liver tissue and in cell culture. Expression of autophagy markers was upregulated in …

Pathologic Inflammation In Malnutrition Is Driven By Proinflammatory Intestinal Microbiota, Large Intestine Barrier Dysfunction, And Translocation Of Bacterial Lipopolysaccharide, Grace T Patterson, Elvia Y Osorio, Alex Peniche, Sara M Dann, Erika Cordova, Geoffrey A Preidis, Ji Ho Suh, Ichiaki Ito, Omar A Saldarriaga, Michael Loeffelholz, Nadim J Ajami, Bruno L Travi, Peter C Melby

Faculty, Staff and Students Publications

Acute malnutrition, or wasting, is implicated in over half of all deaths in children under five and increases risk of infectious disease. Studies in humans and preclinical models have demonstrated that malnutrition is linked to an immature intestinal microbiota characterized by increased prevalence of Enterobacteriaceae. Observational studies in children with moderate acute malnutrition (MAM) have also observed heightened systemic inflammation and increased circulating bacterial lipopolysaccharides (LPS; endotoxin). However, the mechanisms that underpin the systemic inflammatory state and endotoxemia, and their pathophysiological consequences, remain uncertain. Understanding these pathophysiological mechanisms is necessary to design targeted treatments that will improve the unacceptable rate …

Hepatic Pparα Is Destabilized By Sirt1 Deacetylase In Undernourished Male Mice, Ji Ho Suh, Kang Ho Kim, Margaret E Conner, David D Moore, Geoffrey A Preidis

Faculty, Staff and Students Publications

The nutrient sensing nuclear receptor peroxisome proliferator-activated receptor-α (PPARα) regulates the host response to short-term fasting by inducing hepatic transcriptional programming of ketogenesis, fatty acid oxidation and transport, and autophagy. This adaptation is ineffective in chronically undernourished individuals, among whom dyslipidemia and hepatic steatosis are common. We recently reported that hepatic PPARα protein is profoundly depleted in male mice undernourished by a low-protein, low-fat diet. Here, we identify PPARα as a deacetylation target of the NAD-dependent deacetylase sirtuin-1 (SIRT1) and link this to the decrease in PPARα protein levels in undernourished liver. Livers from undernourished male mice expressed high levels …

Adult Food Protein-Induced Enterocolitis Syndrome, Sara Anvari, Melanie A Ruffner

Faculty, Staff and Students Publications

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE, cell-mediated food allergy, commonly diagnosed in infants and young children. In recent years, new-onset adult FPIES has been recognized. The underlying pathogenic mechanism of FPIES has yet to be elucidated, thus disease-specific diagnostic biomarkers have yet to be determined and an oral food challenge (OFC) remains the gold-standard for the diagnosis. Pediatric patients with FPIES classically present with symptoms of delayed, repetitive vomiting approximately 1 to 4 hours following ingestion of a food allergen. However, adults with FPIES have been reported to have a different symptom profile and different food triggers compared …

Factors Impacting Vaccine Uptake During Pregnancy: A Retrospective Analysis, Maame Aba Coleman, Deepa Dongarwar, Jessica Ramirez, Mei-Li Laracuente, Chelsea Livingston, Julliet Ogu, Racquel Lyn, Arabella Hall, Sylvia Adu-Gyamfi, Hamisu M Salihu

Faculty, Staff and Students Publications

BACKGROUND AND OBJECTIVE: Vaccine uptake rates during pregnancy remain below target goals due to a convergence of factors. In particular, women of lower socioeconomic means and racial minorities typically have reduced rates of vaccine acceptance. This study aims to identify additional factors contributing to vaccine acceptance within a sample population of women receiving prenatal care in Houston, Texas, United States of America.

METHODS: We performed a retrospective cross-sectional analysis of 11,500 pregnant women covered by Medicaid or ChipPerinate who received prenatal care during 2013-2021, assessing influenza (flu) and combined Tetanus, Diphtheria, Acellular Pertussis (TDAP) vaccine acceptance in the patient population. …

Clinical And Sociodemographic Characteristics Associated With Emergency Peripartum Hysterectomy Due To Puerperal Sepsis In Malawi, Mary Stokes, Amber Olson, Clare Algeo, Bakari Rajab, Carolyn Mwalwanda, Deepa Dongarwar, Rachel Pope

Faculty, Staff and Students Publications

BACKGROUND AND OBJECTIVE: In Malawi, emergency peripartum hysterectomy continues to be routine for the management of puerperal sepsis. While the hysterectomy may be life-saving for the mother, it carries with it life-altering permanent sterility. The surgeon is left with a difficult dilemma: remove the infection source (uterus) to preserve the life of the patient at the cost of her fertility, or preserve the uterus and fertility but risk worsening infection and possible death for the patient. The objective of this study was to (1) identify characteristics associated with mortality post-laparotomy due to puerperal sepsis and (2) identify characteristics associated with …

Single-Port Laparoscopic Sacrospinous Ligament Suspension Via The Natural Vaginal Cavity (Svnotes) For Pelvic Prolapse: The First Feasibility Study, Yuanyuan Lyu, Huafeng Ding, Jin Ding, Yonghong Luo, Xiaoming Guan, Guantai Ni

Faculty, Staff and Students Publications

Objective

This study aims to investigate the feasibility and short-term efficacy of single-port laparoscopic-assisted transvaginal natural cavity endoscopic sacrospinous ligament suspensions (SvNOTES).

Methods

A total of 30 patients diagnosed with anterior or/and middle pelvic organ prolapse Stages III and IV underwent natural vaginal cavity (SvNOTES), and 30 patients who underwent conventional sacrospinous ligament (SSLF) were used as a control group. The operation time, blood loss, postoperative POP-Q score, length of hospital stay, and complications were compared between the two groups.

Results

The operation time for SvNOTE was (60 ± 13) min, which was longer than (30 ± 15) min for …

Evaluation Of The Clinical Effectiveness Of Modified Sacrospinous Ligament Fixation, Yuanyuan Lyu, Huafeng Ding, Ying Zhang, Suhua Shi, Jin Ding, Chengcheng Zhu, Xiaoming Guan, Guantai Ni, Yonghong Luo

Faculty, Staff and Students Publications

OBJECTIVE: To describe the surgical techniques and short-term outcomes for 50 cases of modified sacrospinous ligament fixation

METHODS: 100 patients with pelvic organ prolapse (stage III or stage IV based on POP-Q staging) from January 2018 to January 2020 were retrospectively analyzed. Among them, 50 patients received modified sacrospinous ligament fixation via the anterior vaginal wall path for pelvic organ prolapse (mSSLF group), while the other 50 patients received pelvic reconstruction using T4 mesh (T4 group). Operative time, blood loss, postoperative POP-Q score, length of the hospital stay, complications, and postoperative pain were compared between the two groups.

RESULTS: The …

"It Just Kind Of Feels Like A Different World Now:" Stress And Resilience For Adolescents With Type 1 Diabetes In The Era Of Covid-19, Maeve B O'Donnell, Marisa E Hilliard, Viena T Cao, Miranda C Bradford, Krysta S Barton, Samantha Hurtado, Brenda Duran, Samantha Garcia Perez, Kiswa S Rahman, Samantha Scott, Faisal S Malik, Daniel J Desalvo, Catherine Pihoker, Chuan Zhou, Abby R Rosenberg, Joyce P Yi-Frazier

Faculty, Staff and Students Publications

PURPOSE: The COVID-19 pandemic has been a major stressor for adolescents. Given the unique implications of the pandemic for youth with type 1 diabetes (T1D), who already navigate multiple stressors as a function of their chronic condition, we aimed to describe the impact of the pandemic on adolescents with T1D and describe their coping strategies and resilience resources.

RESEARCH METHOD: In a 2-site (Seattle WA, Houston TX) clinical trial of a psychosocial intervention targeting stress/resilience, adolescents 13-18 years old with T1D ≥ 1 year and elevated diabetes distress were enrolled August 2020 - June 2021. Participants completed a baseline survey …

Adrenomedullin And Its Receptors Are Expressed In Mouse Pancreatic Β-Cells And Suppresses Insulin Synthesis And Secretion, Yuanlin Dong, Simone Hernandez Ruano, Akansha Mishra, Kathleen A Pennington, Chandrasekhar Yallampalli

Faculty, Staff and Students Publications

Gestational diabetes mellitus (GDM) is associated with defective pancreatic β-cell adaptation in pregnancy, but the underlying mechanism remains obscure. Our previous studies demonstrated that GDM women display increased plasma adrenomedullin (ADM) levels, and non-obese GDM mice show decreased serum concentrations of insulin and the number of β-cells in pancreas islets. The aims of this study is to examine if ADM and its receptors are expressed in female mouse pancreas, and if so, whether insulin secretion is regulated by ADM in mouse β-cell line, NIT-1 cells and isolated mouse pancreatic islets. Present study shows that ADM and its receptor components CRLR, …

Lipid Dysfunction And Adrenomedullin Expression In Omental Versus Subcutaneous Adipose Tissues In Diabetic Pregnancies, Yuanlin Dong, Ancizar Betancourt, Michael A Belfort, Chandrasekhar Yallampalli

Faculty, Staff and Students Publications

Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy but the underlying mechanism remains obscure. The aims of this study are to examine if omental adipose tissue (OMAT) and subcutaneous AT (SCAT) differentially express proinflammatory and lipid metabolic adipokines, and if so, whether their regional differences have implications on lipid metabolism in GDM. Paired samples of OMAT and SCAT were excised from pregnant women in scheduled Cesarean sections with non-obese (NOBS), obese (OBS) and GDM. The results showed that the mRNA of monocyte chemoattractant protein (MCP)-1, macrophage marker CD68, and cytokines IL-6, IL-8, and TNF-α are …

Systematic Profiling Of Dnmt3a Variants Reveals Protein Instability Mediated By The Dcaf8 E3 Ubiquitin Ligase Adaptor, Yung-Hsin Huang, Chun-Wei Chen, Venkatasubramaniam Sundaramurthy, Mikołaj Słabicki, Dapeng Hao, Caroline J Watson, Ayala Tovy, Jaime M Reyes, Olga Dakhova, Brielle R Crovetti, Christina Galonska, Minjung Lee, Lorenzo Brunetti, Yubin Zhou, Katrina Tatton-Brown, Yun Huang, Xiaodong Cheng, Alexander Meissner, Peter J M Valk, Lionel Van Maldergem, Mathijs A Sanders, Jamie R Blundell, Wei Li, Benjamin L Ebert, Margaret A Goodell

Faculty, Staff and Students Publications

Clonal hematopoiesis is a prevalent age-related condition associated with a greatly increased risk of hematologic disease; mutations in DNA methyltransferase 3A (DNMT3A) are the most common driver of this state. DNMT3A variants occur across the gene with some particularly associated with malignancy, but the functional relevance and mechanisms of pathogenesis of the majority of mutations are unknown. Here, we systematically investigated the methyltransferase activity and protein stability of 253 disease-associated DNMT3A mutations, and found that 74% were loss-of-function mutations. Half of these variants exhibited reduced protein stability and, as a class, correlated with greater clonal expansion and acute …

Il-17 Producing Lymphocytes Cause Dry Eye And Corneal Disease With Aging In Rxrα Mutant Mouse, Jehan Alam, Ghasem Yazdanpanah, Rinki Ratnapriya, Nicholas Borcherding, Cintia S De Paiva, Dequan Li, Rodrigo Guimaraes De Souza, Zhiyuan Yu, Stephen C Pflugfelder

Faculty, Staff and Students Publications

PURPOSE: To investigate IL-17 related mechanisms for developing dry eye disease in the Pinkie mouse strain with a loss of function RXRα mutation.

METHODS: Measures of dry eye disease were assessed in the cornea and conjunctiva. Expression profiling was performed by single-cell RNA sequencing (scRNA-seq) to compare gene expression in conjunctival immune cells. Conjunctival immune cells were immunophenotyped by flow cytometry and confocal microscopy. The activity of RXRα ligand 9-cis retinoic acid (RA) was evaluated in cultured monocytes and γδ T cells.

RESULTS: Compared to wild type (WT) C57BL/6, Pinkie has increased signs of dry eye disease, including decreased tear …

Spatial Transcriptomics Of The Lacrimal Gland Features Macrophage Activity And Epithelium Metabolism As Key Alterations During Chronic Inflammation, Olivier Mauduit, Vanessa Delcroix, Takeshi Umazume, Cintia S De Paiva, Darlene A Dartt, Helen P Makarenkova

Faculty, Staff and Students Publications

The lacrimal gland (LG) is an exocrine gland that produces the watery part of the tear film that lubricates the ocular surface. Chronic inflammation, such as Sjögren’s syndrome (SS), is one of the leading causes of aqueous-deficiency dry eye (ADDE) disease worldwide. In this study we analyzed the chronic inflammation in the LGs of the NOD.B10Sn-H2b/J (NOD.H-2b) mice, a mouse model of SS, utilizing bulk RNAseq and Visium spatial gene expression. With Seurat we performed unsupervised clustering and analyzed the spatial cell distribution and gene expression changes in all cell clusters within the LG sections. Moreover, for the …

New, Potent, Small Molecule Agonists Of Tyrosine Kinase Receptors Attenuate Dry Eye Disease, Zhiyuan Yu, Shaon Joy, Tianxiong Mi, Ghasem Yazdanpanah, Kevin Burgess, Cintia S De Paiva

Faculty, Staff and Students Publications

Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin3 (NT-3) bind to tyrosine kinase (Trk) receptors, TrkA, TrkB, and TrkC, respectively. This study investigated the efficacy of novel molecule agonists of Trk receptors in an in vivo model of dry eye disease (DED). Small molecule TrkC agonist (C1) and a pan-Trk agonist (pan) were synthesized for this. C57BL/6J mice were subjected to desiccating stress (DS) and received bilateral eye drops of C1, pan, or vehicle (2x/day). Dry eye signs, inflammation and expression of corneal barrier function, and conjunctival goblet cell (GC) densities were measured as part of the DED …

Cathepsin S Is A Novel Target For Age-Related Dry Eye, Zhiyuan Yu, Jinmiao Li, Gowthaman Govindarajan, Sarah F Hamm-Alvarez, Jehan Alam, De-Quan Li, Cintia S De Paiva

Faculty, Staff and Students Publications

Cathepsin S (CTSS) is a protease that is proinflammatory on epithelial cells. The purpose of this study was to investigate the role of CTSS in age-related dry eye disease. Ctss−/− mice [in a C57BL/6 (B6) background] of different ages were compared to B6 mice. CTSS activity in tears and lacrimal gland (LG) lysates was measured. The corneal barrier function was investigated in naïve mice or after topical administration of CTSS eye drops 5X/day for two days. Eyes were collected, and conjunctival goblet cell density was measured in PAS-stained sections. Immunoreactivity of the tight junction proteins, ZO-1 and occludin, was …

Metabolic Targeting, Immunotherapy And Radiation In Locally Advanced Non-Small Cell Lung Cancer: Where Do We Go From Here?, Annika Dhawan, Phillip M Pifer, Vlad C Sandulache, Heath D Skinner

Faculty, Staff and Students Publications

In the US, there are ~250,000 new lung cancer diagnoses and ~130,000 deaths per year, and worldwide there are an estimated 1.6 million deaths per year from this deadly disease. Lung cancer is the most common cause of cancer death worldwide, and it accounts for roughly a quarter of all cancer deaths in the US. Non-small cell lung cancer (NSCLC) represents 80-85% of these cases. Due to an enormous tobacco cessation effort, NSCLC rates in the US are decreasing, and the implementation of lung cancer screening guidelines and other programs have resulted in a higher percentage of patients presenting with …